IBS is a syndrome defined as a functional disorder in which abdominal symptoms consisting mainly of abdominal pain and irregular bowel movement continue but organic disorders as causes therefor cannot be identified (Clinical Gastroenterology, 2000, VOL. 15, No. 13, p. 1607). It is often associated with psychological manifestations such as anxiety and depression.
According to Rome II which are diagnostic criteria for all the functional digestive disorders, when “no organic disorders are found in spite of the existence of lower gastrointestinal symptoms”, such a condition is diagnosed as functional bowel disorders. The functional bowel disorders are divided further into IBS, functional diarrhea, functional constipation, and functional abdominal bloating based on their characteristic syndromes. In brief, the functional diarrhea is chronic diarrhea not accompanied with abdominal pain, the functional constipation is chronic constipation not accompanied with abdominal pain and the functional abdominal bloating is a group of disorders having not abdominal pain but abdominal distension and gas as cardinal symptoms (Clinical Gastroenterology, 2000, VOL. 15, No. 13, p. 1698). IBS is a disorder which is not included in any one of the functional diarrhea, functional constipation and functional abdominal bloating so that it can be considered as a generic name of diarrhea accompanied with abdominal pain (diarrhea predominant IBS), constipation accompanied with abdominal pain (constipation predominant IBS), and disorders (alternating IBS) which are accompanied with abdominal pain, and alternating diarrhea and constipation.
At present, there exists no eradicative drug for IBS and symptomatic treatment have been conducted for aiming at amelioration of symptoms of each disorder. Each type of IBS will next be described more specifically. In diarrhea predominant IBS, frequent diarrhea with small volumes of stool occurs continuously over a long period. For this diarrhea predominant IBS, an anticholinergic agent capable of controlling the contraction of smooth muscle and having antispastic action has been popularly employed. In many cases, antiflatulents are used in combination. Constipation predominant IBS is spastic constipation caused by acceleration of the bowel motility. For this constipation predominant IBS, a method of adjusting the hardness of stool by using a saline laxative is frequently employed. In alternating IBS, diarrhea and constipation occur alternately. It is therefore difficult to treat it with one drug and usually a prokinetic agent is employed.
Japanese Patent Unexamined Publication (Kokai) No. Hei 5-310747 discloses that the compounds of the present invention enhance the gastric motility, more specifically, the compounds of the present invention accelerate gastric emptying in male ddy mice, accelerate gastric contraction in the dog with a strain gauge force transducer attached thereto, and have 5-HT3 (serotonin 3) receptor antagonistic activity in the Bezold-Jarisch reflex test. This publication however includes neither suggestion nor teaching on the relationship between the compounds of the present invention and bowel function.
Japanese Patent Unexamined Publication (Kokai) No. Hei 8-143573 discloses an invention concerning a preventive or therapeutic agent for diseases of intestinal motility dysfunction, which comprises, as an active ingredient, the above-described thieno[3,2-b]pyridinecarboxamide compound. Specific examples of the diseases of intestinal motility dysfunction include atonic constipation, spastic constipation and rectal constipation. Only Example 2 of Japanese Patent Unexamined Publication (Kokai) No. Hei 8-143573, however, directly shows that the compound is effective for constipation. A disease model used in this example should be an atonic constipation model, because clonidine for relaxing intestine was applied as the drug thereto. This publication only suggests that the compound of the present invention is effective for atonic constipation and does not include a specific disclosure about the effectiveness of the compound for constipation predominant IBS (as described above, constipation predominant IBS can be considered as spastic constipation)
On the contrary the present invention has firstly and experimentally revealed that the specific thieno[3,2-b]pyridinecarboxamide compounds are effective against the constipation predominant IBS by administering said compounds to human constipation predominant IBS patients.
The purpose of the present invention is to provide to a medicament for preventing and/or treating constipation predominant IBS containing the specific thieno[3,2-b]pyridinecarboxamide compounds as the active ingredients.